Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Mouth Neoplasms

Pharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Mouth Diseases

Stomatognathic Diseases

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Cetuximab

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction.

Intensity Modulated Radiation Therapy

chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion

chemotherapy

David Sher, MD, MPH

This study aims to significantly improve the acute and late morbidity of patients with oropharyngeal and laryngeal squamous cell carcinoma both by tailoring the elective irradiation only to regions with a legitimate risk of recurrence (\> 5%) and by lowering the elective dose to 40 Gy. Level IB will not be electively treated unless it is involved with pathologic or suspicious lymphadenopathy. Level V will not be treated unless two or more ipsilateral nodal levels are involved (or level V itself has pathologic or suspicious adenopathy). Levels III and IV will only be irradiated if the immediately proximal level contains pathologic lymphadenopathy (i.e. level III irradiated if level II is positive; level IV irradiated if level III is positive). We anticipate that this approach should dramatically improve the acute and late complication profile.

Involved Field Elective Volume De-Intensification Radiation Therapy for Head and Neck Cancer

A Prospective Phase II Study of Involved Field Elective Volume De-Intensification for Oropharyngeal and Laryngeal Squamous Cell Carcinoma Treated With Intensity Modulated Radiation Therapy

The crude risk of 2-year solitary elective volume recurrence will be calculated among all patients who are followed for at least 2 years. Patients who die before 2 years without an SEVR will be included in the denominator.

Quality of life (QOL) patient-reported outcomes (PRO) for overall number of participants following treatment with elective volume and dose de-escalation, using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), EORTC HN35, which is specific to head and neck cancer, and composite MD Anderson Dysphagia Inventory (MDADI).

EORTC QLQ-C30 and QLQ-H\&N35 are scored on a 4-point categorical scale ranging from 1 "not at all" to 4 "very much". This scale is then linearly transformed to a 0-100 scale, where a higher score represents a higher response level. A high score for a functional scale represents higher level functioning, a high score for quality of life represents a high quality of life, and a high score for a symptom scale represents worse symptoms.

MD Anderson Dysphagia Inventory (MDADI) questionnaire: Possible score ranges from 0-100, with higher score indicating higher functioning.

Only adverse events (grade 3-5) assessed to be definitely, probably, or possibly related to protocol treatment up to 2 years post-treatment will be considered. This was measured according to NCI's CTCAE v4.0 toxicity criteria.

The prevalence of gastrostomy use up to 2 years will be described.

The average patient utilities (derived from EQ-5D) from baseline up to 2 years from the end of treatment will be described. Changes in patient utility will be analyzed using generalized estimated equations (GEE).

Overall survival will be calculated from the initiation of treatment using the Kaplan-Meier method.

Progression-free survival will be calculated from the initiation of treatment. Progression is confirmed by biopsy, which will be used as the date of progression.

The percentage of patients with locoregional or distant failure within 2 years of treatment will be estimated using cumulative incidence statistics, with death serving as the competing risk. Cumulative incidence refers to the estimated risk/probability of tumor failure within 2 years of treatment, either locoregional recurrence or distant metastasis, accounting for the competing risk of death.

University of Texas Southwestern Medical Center

Professor of Medicine

Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction.

chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion

Radiation Therapy

Age, Continuous

Sex: Female, Male

White

Black

Hispanic

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

Oropharynx

Larynx

Disease site

Dr. David Sher

Number of Patients With Solitary Elective Volume Recurrence

EORTC QLQ30 global

EORTC QLQ30 physical fcn

EORTC QLQ30 role fcn

EORTC QLQ30 emotional fcn

EORTC QLQ30 cognitive fcn

EORTC QLQ30 social fcn

EORTC HN35 dry mouth

EORTC HN35 sticky saliva

EORTC HN35 senses

EORTC HN35 pain

EORTC HN35 speech

Composite MDADI

Total Cohort Baseline

Total Cohort 3 Month

Total Cohort 6 Month

Total Cohort 12 Month

Quality of Life (QOL) Patient Reported Outcomes (PRO)

Number of Participants With Definite, Possible, and Probable Protocol-related Toxicities (Grade 3-5)

Total Number of Participants With Gastrostomy Dependence

Collected data were not considered valid due to software limitations as it was not available to auto-calculate the data as proposed by our EMR

Patient Utilities

Reported the percentage of the total patient population who survived to 2 years post-treatment.

Overall Survival

Percentage of the total patient population with progression-free survival 2 years post treatment

Progression-free Survival

Locoregional recurrence

Distant metastasis

Probability of Locoregional or Distant Tumor Failure

Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel). There was only one study arm. The radiation field and dose are the same with or without chemotherapy. The intent is to assess the effects of radiation therapy, regardless of chemotherapy treatment.

Intensity Modulated Radiation Therapy: The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction.

chemotherapy: chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion

Overall Study

Oral Squamous Cell Carcinoma

Trametinib

Protein Kinase Inhibitors

Enzyme Inhibitors

GSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.

Trametinib (GSK1120212) is a selective MEK1 and MEK2 inhibitor with selective activity towards BRAF and RAS mutant cancer cell lines and hematopoietic cancer cells from AML and CML origins.

GSK1120212

Douglas Adkins, M.D.

This phase II trial studies how trametinib effects tumor cells in patients with oral cavity squamous cell carcinoma that can be removed by surgery. Trametinib may shrink the tumor by blocking an enzyme pathway needed for cell growth.

The rationale for this study in oral cavity squamous cell carcinomas rests on pre-clinical findings demonstrating that (a) activation of the ERK1/2 kinases is associated with aggressive features, (b) this aggressive phenotype is directly linked to expression of CD44, a cell surface hyaluronan receptor and (c) this association between activated ERK1/2 and CD44 is also identified in human cell lines and primary tumors. These data suggest that ERK1/2 is targetable biochemical pathway in CD44 expressing cells. These cells represent putative cancer stem cells or tumor initiating cells that have been associated with worse patient outcomes. Thus, the application of GSK1120212 to target OCSCC is a specific translational application of our laboratory findings.

GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

A Phase II Window of Opportunity Trial With GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

Pre-post measure of p-EKP expression was measured by change in staining intensity and quartile distribution.

Pre-post measure of CD44 expression using IHC.

Clinical Response was evaluted by quantitative changes in tumor size based on clinical examination of area of tumor at baseline and after GSK1120212 based on two dimensional measurements.

Peripheral blood - baseline and Day 14

Tumor - baseline and Day 15

Number of adverse events were monitored for 30 day following last dose of GSK1120212

Intratumarol metabolic changes were evaluated by changes in in SUVmax in the primary tumor; quantitative analysis SUVmax with the primary tumor site was determined within a volume of interest around the tumor using a Siemens eSoft workstation.

National Comprehensive Cancer Network

Washington University School of Medicine

AE grade 3 or higher will be followed for 3-6 months and considered at least possibly related

GSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.

GSK1120212: Trametinib (GSK1120212) is a selective MEK1 and MEK2 inhibitor with selective activity towards BRAF and RAS mutant cancer cell lines and hematopoietic cancer cells from AML and CML origins.

Median Age (years)

Age, Customized

Gender

Race (NIH/OMB)

Tongue

Floor of Mouth

Retromolar trigone

Buccal

Oral Cavity Sub-Site

Stage II

Stage III

Stage IV

Cancer staging uses the TNM system where T=primary tumor, N stands for nodes (indicating cancer has spread to lymph nodes, and M for metastasis. Numbering associated with staging or letters denotes an increase in number, size, location or severity. Stage II (T2N0) Stage III (T2N1, T3N1) Stage IV(T2N2a,T2N2b,T3N2b,T4aN0,T4aN1,T4aN2b,T4aN2c)

Clinical Stage

History of Smoking and/or Alcohol Abuse

Small number of treated patients. Short duration of GSK1120212 administration. Biopsy limitations precluded analysis of all patients.

Dr. Douglas Atkins

Decrease in p-EPK1/2 expression

Inverse relationship in p-EPK expression

No change in p-EKP expression

Increase in p-EKP expression

Only15 of the 17 participants had sufficient pre- and post-treatment biopsies with sufficient tumor content to be evaluated for this biomarker assessment.

Number of Participants With Changes in Putative Tumor Initiating Cell Populations as Defined by Cell Surface CD44 and Intracellular Phospho-ERK1/2 Staining After Treatment With GSK1120212.

Number of Participants With Changes in TumorCell Surface CD44 Expression After Treatment With GSK1120212.

There was an insufficient amount of tissue to collected. The data was not collected and the outcome measure was not analyzed.

Tumor Specific Findings for Pathologic Changes Including Proliferation (Ki-67 Staining), Tumor Vasculature Staining (Microvessel Density), ERK1/2 Mediated Changes in p27 (Kip1) & Flow Cytometric Analysis of the Peripheral Blood & Tumor.

Percentage of Participants With Clinical Response Induced by GSK1120212, as Determined by Change in Tumor Size.

Flow Cytometric Analysis of the Peripheral Blood and Tumor.

Seven patients did not meet protocol-defined tumor size criteria (n=3), withdrew from study (n=3) or declined post GSK1120212 FDG-PET/CT(n=1)

Percent Change in Maximum Standard Uptake Value in Oral Cavity Saqumous Cell Carcinoma (OCSCC) Using F18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT).

Neutrophil decrease (Grade 1-2)

Thrombocytopenia(Grade 1-2)

Colitis( Grade 3-4)

Diarrhea (Grade 1-2)

Mucositis( Grade 3-4)

Nausea (Grade 1-2)

Doudenal Perforation (Grade 3-4)

Stomach Cramps(Grade 1-2)

Lung Infection (Grade 3-4)

Rash, acneiform (Grade 1-2)

Pruritis (Grade 1-2)

Fatigue(Grade 1-2)

Fever (Grade 1-2)

Alkaline Phosphatase (Grade 1-2)

AST (Grade 1-2)

ALT (Grade 1-2)

Blurry Vision (Grade 1-2)

Hypotension (Grade 1-2)

Safety of GSK1120212

Quantitative changes in tumor size based on clinical examination of area of tumor at baseline and after GSK1120212 based on two dimensional measurements.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Involved Field Elective Volume De-Intensification Radiation Therapy for Head and Neck Cancer	NCT03067610	Head and Neck C... Carcinoma, Squa... Neoplasms, Oral Neoplasms, Phar...	Intensity Modul... chemotherapy	18 Years - 99 Years	University of Texas Southwestern Medical Center
GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer	NCT01553851	Neoplasms, Oral Mouth Neoplasms	GSK1120212	18 Years -	Washington University School of Medicine

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